The number of patients diagnosed with prostate cancer has increased 63% in the last 7 years. Over the same time period, the number of deaths has risen from 24,000 to 32,000 cases a year. With the aging of the American male population, these figures can only be expected to increase over the coming years. The answer to lowering the mortality from this disease depends upon our ability to determine its malignant potential, to learn why it is a more aggressive disease in African-Americans that whites, and to determine what governs its response or lack thereof to hormonal therapy. Our hypothesis continues to be that genetic abnormalities will be found at either the RNA or DNA level that determine the natural history of carcinoma of the prostate (CaP). Our studies will continue to identify and assess the prevalence of these genetic abnormalities, or their manifestations, in benign, premalignant, and malignant prostate tissues. We will continue to characterize CaP by using the polymerase chain reaction technique, focusing on studies of p53, Rb-1, nm23, hAR, and ras. Selected samples will then be sequenced in order to determine point mutations. We will, over the grant period, expand our studies to include the techniques of DGGE and subtractive hybridization. We will continue to develop tissue culture capabilities in order to supply samples of both hormonally-manipulated amd unmanipulated tissue for our molecular studies. The chance of success in these endeavors will be greatly enhanced by being a member of the proposed cooperative network, since this will allow for interchange of ideas, materials, and techniques. Thus, it will be possible to much more rapidly validate findings from individual laboratories by comparing results of the molecular tests with each other and to known clinical parameters. Evaluation of the molecular studies, both individually and collectively, will be accelerated, leading to a more rapid, cost- effective characterization of CaP and, from there, to answers to the questions posed in the RFA.